Insulin secretion occurs within Islets of Langerhans of the neuroendocrine pancreas. The series of cellular events leading to insulin secretion is very complex, reflecting its importance in glucose homeostasis. Proteins may be involved in the dynamic translocation of channels and other signaling molecules in glucose stimulated insulin secretion, such as ERM proteins. ERM proteins (Ezrin, Radixin, and Moesin) are a family of proteins that functionally link the actin cytoskeleton with the plasma membrane. This family of proteins becomes activated through phosphorylation by Akt2 at a critical threonine on the C- terminus, relieving ERM autoinhibition and allowing them to act as scaffolding molecules. ERM proteins have been implicated in the translocation of channels to the plasma membrane upon stimulation in other cell types. Insulin secretion occurs through the interaction of numerous channels and these channels may translocate as well. ERM proteins have not been investigated in insulin secreting cells, but may be quite important in their physiology. We have recently deomonstrated their presence and activation in pancreatic beta cells. This research will address the role of ERM proteins in insulin secretion and beta cell physiology. [unreadable] [unreadable] [unreadable]